Understanding the metabolism, distribution, and elimination of chemical xenobiotics is often critical to an appreciation of their toxic effects. Extrapolation of results from animal testing to possible human health effects requires knowledge of metabolic pathways and of in vivo kinetic behavior. Investigation of mechanistic aspects of metabolic processes allow greater understanding of how metabolism of a xenobiotic might lead either to detoxification or to a reactive metabolite with greater toxicity. As more is learned about mechanisms of metabolism, more accurate predictions of possible metabolic pathways for new compounds should be possible, This group carried out studies on cyclohexanone oxime (CHOX), furan, oxazepam (OXM), tris(2-chloroethyl) phosphate (TRCP), and propetamphos (PROP) In the past year. CHOX an intermediate in Nylon production, was rapidly metabolized to glucuronide conjugates of mono- and dihydroxycyclohexanes. Furan-derived radioactivity was evenly distributed between heme and protein moieties of cytochromes P-450 following microsomal incubations. Preliminary results indicate that Swiss-Webster, that mouse strain that appears to be more sensitive to the tumorigenic effect of OXM has a greater ability to metabolize OXM. The identity of four metabolites from Swiss-Webster and B6C3Fl mice has been verified. Pharmacokinetic parameters for TRCP, a flame retardant, have been determined in male and female rats. No significant gender differences in the parameters were found. TRCP is being used as a model compound in development of a microdialysis/mass spectrometry system to determine plasma concentrations of xenobiotics and metabolites. Pharmacokinetics of PROP, an organophosphate insecticide, have been investigated. PROP is rapidly cleared from plasma with a half-life of 53 and 30 min for male and female rats respectively. Although these differences were not significant at the p = 0.05 level (n = 6), there was an obvious clinical gender difference in susceptibility to PROP toxicity: the females being more susceptible.